Nodulisporic Acid A, a Novel and Potent Insecticide from a Nodulisporium Sp. Isolation, Structure Determination, and Chemical Transformations

• Published in: Journal of the American Chemical Society Vol. 119; no. 38; pp. 8809 - 8816
• Main Authors: Ondeyka, John G, Helms, Gregory L, Hensens, Otto D, Goetz, Michael A, Zink, Deborah L, Tsipouras, Athanasios, Shoop, Wesley L, Slayton, Lyndia, Dombrowski, Anne W, Polishook, Jon D, Ostlind, Dan A, Tsou, Nancy N, Ball, Richard G, Singh, Sheo B
• Format: Journal Article
• Language: English
• Published: American Chemical Society 24-09-1997
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja971664k

The potent insecticidal agent nodulisporic acid A (1a), representative of a new class of indole terpenes, was isolated from fermentations of a Nodulisporium sp. Nodulisporic acid A was active against the larvae of the blowfly and mosquito at sub-part-per-million levels. The structure followed mainly from a consideration of spectroscopic evidence, including Dunkel's computerized 2D INADEQUATE analysis. The relative stereochemistry of the eastern and western hemispheres of 1a and its methyl ester, 1b, were independently determined on the basis of ROESY, NOESY, NOEDS, and J vic evidence. By employing the same methods, the complete relative stereochemistry was determined by analysis of suitable transformation products, using the reduced β-ketodihydropyrrole ring as a stereochemical bridge between the two zones. These results were confirmed by X-ray analysis of the 7-p-bromobenzoate methyl ester derivative, 1c. The absolute stereochemistry was established by application of the advanced Mosher method to methyl ester 1b. Of biogenetic interest is the presence of a unique isoprenylated indole moiety not previously found in other indole mycotoxins.